title: ADAMTS13 content in plasma-derived factor VIII/von Willebrand factor concentrates.
abstract: Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome caused by a congenital or acquired deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor (VWF) and thus prevents the formation of platelet-rich thrombi in the microcirculation. TTP can be fatal if not appropriately and timely treated with the infusion of fresh frozen plasma (FFP) or exchange plasmapheresis, that reverse the process of microangiopathy by removing anti-ADAMTS13 autoantibodies and replacing functional ADAMTS13. The treatment of TTP with FFP is not free from risks and must be administered in hospitals or clinics, owing to the substantial amount of plasma volume infused or exchanged and the frequent need of catheter application. Moreover, most FFPs are not subjected to treatments to remove or inactivate blood-borne infectious agents. A number of recent reports indicate that certain plasma-derived VWF-factor VIII (FVIII) concentrates are clinically effective in the treatment of congenital TTP. In this study, we measured ADAMTS13 levels in various plasma-derived VWF-FVIII concentrates, showing that Koate(®) -DVI (Grifols), contained relatively high amounts of ADAMTS13 and that Alphanate(®) (Grifols) was the closest other product in terms of protease content. Koate(®) -DVI contains, on average (five lots tested), 0.091 ± 0.007 Units of ADAMTS13 activity per IU of FVIII. On the basis of this analysis and other reports of VWF-FVIII concentrate utilization in congenital TTP, potential dosing, and future clinical developments are discussed.
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, University of Milan, Luigi Villa Foundation, Milan, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.forename: Pier M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: Carla
authors.initials: C
authors.lastname: Valsecchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontiggia
authors.forename: Claudio
authors.initials: C
authors.lastname: Farina
authors.forename: Anastassios D
authors.initials: AD
authors.lastname: Retzios
mesh_terms: D051722:ADAM Proteins / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D000071120:ADAMTS13 Protein; D001323:Autoantibodies / Q000097:blood; D005169:Factor VIII / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D010949:Plasma / Q000737:chemistry* / Q000378:metabolism; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000628:therapy; D014841:von Willebrand Factor / Q000032:analysis* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D001323:Autoantibodies; D014841:von Willebrand Factor; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human